Populations all over the world are experiencing rapid increases in the prevalence of obesity and diabetes. To date, the public health response to the emerging obesity epidemic has been almost totally ineffective. Professional bodies and governments have issued prevention guidelines, all of which include recommendations on levels of physical activity. However, it is not clear that the current recommendations to increase physical activity would reverse the trend in age-related weight gain. In fact, there is virtually no direct evidence that can be brought to bear on the question of whether the obesity epidemic has resulted primarily or even partially from society-wide declines in habitual physical activity. Our objectives with this project are to examine whether an individuals' amount of activity energy expenditure (AEE) is related to adiposity and adiposity/diabetes-related hormones in a diverse sample of 2500, and to test the ecological hypothesis that a decline in levels of AEE is an important cause of the increases in obesity that are currently taking place in many societies. Our aim is to use doubly labeled water and/or accelerometers to objectively measure activity energy expenditure in community samples from five adult populations across the spectrum of obesity risk. From each site, i.e., Nigeria, South Africa, Seychelles, Jamaica and the US, 500 black adults will be recruited. In all participants, AEE will be measured using accelerometers and in a subset of 75 per site, AEE will also be measured by doubly labeled water. The doubly labeled water sample will be used to confirm site-specific concordance with the accelerometer measurements and to estimate population mean levels of AEE. In addition, body composition, dietary intake, fasting glucose, insulin, adiponectin, leptin and ghrelin will assessed. The relationships between calories expended in activity and body composition, dietary intake, glucose, hormones and adipocytokines, both within and between each population using doubly labeled water and accelerometers will be examined. Weight will be measured at 12 and 24-months and AEE by accelerometer will be assessed again at 2-years of follow-up and associations between change in AEE and change in weight assessed. The central purpose of our proposed project is to test whether AEE or change in AEE can be identified as a contributory mechanism to population- wide weight gain and, if so, to quantify its importance. In addition, we seek to understand the interrelationships between the adipocytokines and the hormones ghrelin and insulin, and EE in the regulation of body weight across the continuum of BMI represented by these five populations. PUBLIC HEALTH RELEVANCE Guidelines for the amount of physical activity that might prevent obesity have taken on considerable public health importance. To date, however, measurement of physical activity has been very crude. We propose to conduct a large international study to define the impact of daily activity level on the risk of weight gain and obesity.